Neoplasms

All Conditions

Rare Diseases

Neuroblastoma

Neuroectodermal Tumors, Primitive, Peripheral

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Neuroepithelial

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

All Drugs and Chemicals

Antineoplastic Agents

Micronutrients

Anti-Infective Agents

Antibodies

Antibodies, Monoclonal

Molgramostim

Sargramostim

Immunoglobulins

Iodine

Dinutuximab

Vorinostat

3-Iodobenzylguanidine

Immunologic Factors

Histone Deacetylase Inhibitors

Enzyme Inhibitors

Radiopharmaceuticals

Patients will receive 131I-MIBG on day 1. Dinutuximab is given intravenously on days 8-11 and 29-32 of therapy. Dinutuximab and 131I-MIBG dose will be based on the dose level assigned at the time of patient registration. Patient will receive GM-CSF on days 8-17 and 29-38 at 250 mcg/m2. All patients will receive autologous hematopoietic stem cell infusion on day 15 (+/- 2) of therapy

Patients will receive vorinostat on days 0-13. 131I-MIBG will be received on day 1. Dinutuximab is given intravenously on days 8-11 and 29-32 of therapy. Dinutuximab and 131I-MIBG dose will be based on the dose level assigned at the time of patient registration. Patient will receive GM-CSF on days 8-17 and 29-38 at 250 mcg/m2. All patients will receive autologous hematopoietic stem cell infusion on day 15 (+/- 2) of therapy

Patients will receive 131I-MIBG on day 1. 131I-MIBG dose will be based on the dose level assigned at the time of patient registration

131I-MIBG

Dinutuximab is given intravenously on days 8-11 and 29-32 of therapy. Dinutuximab dose will be based on the dose level assigned at the time of patient registration.

Vorinostat will be given on day 0-13. Vorinostat dose will be based on the dose level assigned at the time of patient registration.

Sargramostim (GM-CSF) will be given on day 8-17 at 250 mcg/m\^2

Potassium iodide will be given by mouth at a dose of 6mg/kg 8-12 hours prior to infusion of 131I-MIBG on Day 1 and then 1mg/kg/dose by mouth starting 4-6 hours after completion of MIBG infusion and continuing every 4 hours on protocol days 1-7 and then 1mg/kg/dose by mouth once daily on protocol days 8-45

Potassium Iodide

Thomas Cash, MD

Araz Marachelian, MD, MS

131I-Metaiodobenzylguanidine (131I-MIBG) is one of the most effective therapies utilized for neuroblastoma patients with refractory or relapsed disease. In this pediatric phase 1 trial, 131I-MIBG will be given in combination with dinutuximab, a chimeric 14.18 monoclonal antibody. This study will utilize a traditional Phase I rolling 6 dose escalation design to determine a recommended phase 2 pediatric dose. An expansion cohort of an additional 6 patients will then be enrolled. If tolerable, vorinostat will then be added to the third dose level. A 6 patient expansion cohort may then be enrolled.

131I-Metaiodobenzylguanidine (131I-MIBG) is one of the most effective therapies utilized for neuroblastoma patients with refractory or relapsed disease. Data from pre-clinical and adult studies suggest that radiation can enhance the efficacy of immunotherapy and targeted therapies such as dinutuximab. This first pediatric phase 1 trial of 131I-MIBG in combination with dinutuximab and vorinostat aims to determine the recommended phase 2 pediatric dose of these three therapies in combination.

MIBG With Dinutuximab +/- Vorinostat

A Phase I Study of 131I-MIBG With Dinutuximab +/- Vorinostat for Relapsed/Refractory Neuroblastoma

Proportion of patients with Course 1 DLT in Cohort A

Proportion of patients with Course 1 DLT in Cohort B

Proportion of patients with any grade 3 or greater non-hematological toxicities in Cohort A

Proportion of patients with any grade 3 or greater non-hematological toxicities in Cohort B

Proportion of patients evaluable for response with a best overall response of CR/CR-MD/PR for patients in Cohort A

Proportion of patients evaluable for response with a best overall response of CR/CR-MD/PR for patients in Cohort B

United Therapeutics

New Approaches to Neuroblastoma Therapy Consortium

Pheochromocytoma

Paraganglioma

Neuroendocrine Tumors

Paragangliomas 1

Neuroendocrine Tumor

Pharmaceutical Solutions

* Minimum dose of 10 mCi/kg for patients without a stem cell source whose renal function is above the upper limit of normal but still meets eligibility criteria.
* Dose of 12 mCi/kg for patients without a stem cell source with normal renal function and meets other eligibility criteria.
* Dose of \> 12 mCi/kg to 18 mCi/kg maximum at investigator's discretion for patients meeting eligibility criteria with stem cells available.

131 I-Metaiodobenzylguanidine

For the therapeutic MIBG administration, potassium iodide solution will be administered in a loading dose of 6mg/kg orally at least 8 hours prior to the MIBG injection, and then will be given at 1mg/kg/dose every 4 hours on days 0-6, then 1 mg/kg/day through day 45 post injection.

It is recommended that patients with ANC less than 750 after MIBG infusion begin G-CSF 5 mcg/kg/day subcutaneously (or receive equivalent single dose of Neulasta every 14 days while neutropenic) until neutrophil recovery (generally \>5000). This will start 24 hours after stem cell infusion (if stem cells are to be infused).

G-csf

Tanya Watt, MD

This expanded access is the best available therapy/compassionate use designed to determine the palliative benefit and toxicity of 131I-MIBG in patients with relapsed/refractory neuroblastoma or metastatic pheochromocytoma who are not eligible for therapies of higher priority. Patients may receive a range of doses depending on stem cell availability and tumor involvement of bone marrow. Response rate, toxicity, and time to progression and death will be evaluated.

Primary Objective is to provide access to therapy with 131I-MIBG for patients with relapsed/refractory neuroblastoma or metastatic pheochromocytoma.

Secondary Objectives are to (1) assess disease response to 131I-MIBG therapy for patients with relapsed/refractory neuroblastoma or metastatic pheochromocytoma; (2) gain more information about the toxicities of 131I-MIBG therapy; and (3) assess improvement of symptoms, including pain and fatigue, for patients with relapsed/refractory neuroblastoma or metastatic pheochromocytoma who are receiving 131I-MIBG therapy.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
MIBG With Dinutuximab +/- Vorinostat	NCT03332667	Neuroblastoma	131I-MIBG Dinutuximab Vorinostat Sargramostim Potassium Iodid...	1 Year - 30 Years	New Approaches to Neuroblastoma Therapy Consortium
131I-Metaiodobenzylguanidine (131I-MIBG) Therapy for Relapsed/Refractory Neuroblastoma	NCT03649438	Relapsed Neurob... Metastatic Pheo...	131 I-Metaiodob... Potassium Iodid... G-csf	-	University of Texas Southwestern Medical Center
MIBG With Dinutuximab +/- Vorinostat	NCT03332667	Neuroblastoma	131I-MIBG Dinutuximab Vorinostat Sargramostim Potassium Iodid...	1 Year - 30 Years	New Approaches to Neuroblastoma Therapy Consortium
131I-Metaiodobenzylguanidine (131I-MIBG) Therapy for Relapsed/Refractory Neuroblastoma	NCT03649438	Relapsed Neurob... Metastatic Pheo...	131 I-Metaiodob... Potassium Iodid... G-csf	-	University of Texas Southwestern Medical Center
131I-Metaiodobenzylguanidine (131I-MIBG) Therapy for Relapsed/Refractory Neuroblastoma	NCT03649438	Relapsed Neurob... Metastatic Pheo...	131 I-Metaiodob... Potassium Iodid... G-csf	-	University of Texas Southwestern Medical Center

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